Cyclodextrin inclusion-complexes, enthalpy-entropy

The majority of reported studies of formation of cyclodextrin inclusion complexes in solution have been mainly concerned with determination of the stability constants by using equilibrium spectroscopic techniques, and the measurement of the enthalpy and entropy changes characterizing the complexation reaction. The aim of much of this work has been to determine the driving force of complex-formation. Despite the amount of research in this area, however, no general agreement has been reached, and... 

Fig. 4.—Enthalpy-Entropy Compensation for Alpha Cyclodextrin Inclusion-Complexes. [The guest identification numbers are as given in Table II.]...

A similar complexation study supported by thermodynamic parameters was performed by the same author for mono-(6-anilino-6-deoxy)- 3-cyclodextrin and mono-[ 6-( 1 -pyridinio)-6-deoxy]-P-cyclodextrin complexation with several amino acids in zwitterionic form [24]. The inclusion complexation was enthalpy driven for the former and entropy driven for the latter host. 

Inoue Y, Hakushi T, Liu Y, Tong LH, Shen BJ, Jin DS, Thermodynamics of molecular recognition by cyclodextrins. 1. Calorimetric titration of inclusion complexation of naphthalenesulfonates with a-, f-, and y-cyclodextrins enthalpy-entropy compensation, J. Am. Chem. Soc. 1993 115 475-481. 

We have previously found that solvophobic interactions between side chain moieties of two different ligands co-ordinated to die same metal ion favor mixed complex formation by means of a favorable enthalpy contribution [47-49]. In the CDhm systems the cavity seems to play the same role as a side chain moiety and stereoselectivity is seen to be enthalpy driven. The entropy change seems to be less favorable for the D-enantiomers, the side chains of which are most probably included in the cavity. This could also be interpreted as resulting from the loss of internal rotational freedom of the side chain which predominates over the effect of cavity desolvation due to inclusion. Thermodynamic stereoselectivity was also found in the copper(U) ternary complexes with 6-deoxy-6-[4-(2-aminoethyl)imidazolyl]-p-cyclodextrin 2 (CDmh) [29], an isomer of CDhm, where the histamine is linked by the imidazole nitrogen (Table IE). In this case the copper(II) mixed complex with the D-isomer of tryptophan is less stable than the complex with the L-isomer. 

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